Lecithin-retinol Acyltransferase is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Matthew L. Batten, Yoshikazu Imanishi, Tadao Maeda, Daniel C. Tu, Alexander R. Moise, Darin Bronson, Daniel Possin, Russell N. Van Gelder, Wolfgang Baehr, Krzysztof Palczewski

Research output: Contribution to journalArticle

256 Scopus citations

Abstract

Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are ∼35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.

Original languageEnglish (US)
Pages (from-to)10422-10432
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number11
DOIs
StatePublished - Mar 12 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Batten, M. L., Imanishi, Y., Maeda, T., Tu, D. C., Moise, A. R., Bronson, D., Possin, D., Van Gelder, R. N., Baehr, W., & Palczewski, K. (2004). Lecithin-retinol Acyltransferase is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver. Journal of Biological Chemistry, 279(11), 10422-10432. https://doi.org/10.1074/jbc.M312410200